There is a widely recognized need for an implant material that provides excellent structural support for a variety of clinical applications while providing for osteointegration over acceptable periods of time. Conventional metal implants are designed to ensure mechanical stability of the implanted region to meet short-term mechanical goals but raise a number of longer-term clinical concerns including protuberance over the skin, non-uniform healing, bone atrophy, implant migration and loosening, all of which may lead to a second surgery to remove the implant.
The morbidities associated with metallic implants have stimulated interest in polymeric and resorbable implants compromised of polylactic acid, polyglycolic acid, copolymers thereof, polymethylmethacrylate, polypropylenefumarate, collagen, or collagen-glycoaminoglycans. These devices have not been widely accepted due to a number of clinical complications associated with poor mechanical stability, formation of sinus tracts, osteolysis, synovitis, localized inflammation, and hypertrophic fibrous encapsulation. As a result, a clinical demand for stronger, more biocompatible and resorbable orthopedic implants for use in both load-bearing and non load-bearing applications exists. Such an implant will incorporate a biomaterial possessing the following properties: 1) mechanical stability at the injured site for the required duration to allow adequate healing; 2) biocompatibility with the surrounding host tissue; 3) osteointegration with the host bone; and 4) elimination of aseptic inflammation.
Bioceramics have been identified as biomaterial that may potentially possess the desired properties discussed above. They have found widespread use in craniomaxillofacial, dental, and orthopedic applications as well as oral, plastic, and ear, nose, and throat surgery and are categorized according to their in vivo interaction: bioinert, bioactive, and resorbable. Common bioceramics are alumina, zirconia, calcium phosphate-based ceramics, and glass-ceramic composites.
Bioinert bioceramics include alumina and zirconia, and are characterized as such because the body recognizes them as a foreign object and encapsulates them in fibrous tissue. Furthermore, tissue growth associated with this reaction is used to mechanically fix the inert ceramic article within the body by encouraging tissue ingrowth into surface irregularities or intentionally introduce porosity. Although many ceramic compositions have been tested as implants to repair various parts of the body, few have achieved human clinical application. Problems associated with these ceramics typically involve the lack of a stable interface with connective tissue and/or a mismatch in mechanical properties between the implant and the tissue to be replaced (see Hench in “Bioceramics: from Concept to Clinic,” J. Am. Ceram. Soc., 1991, 74, 1487-1510). In the case of bioinert bioceramic materials, only a physical interdigitation of weak fibrous tissue onto the implant surface is obtained. If the strength of this fixation between the surrounding tissue and implant is insufficient which is often the case, then loosening of the bioceramic can occur causing necrosis of the surrounding tissue along with implant failure. For example, when alumina or zirconia implants are implanted with a tight mechanical fit within the body and movement does not occur at the interface with tissue, the implants can be clinically successful. However, if movement does occur, the fibrous capsule surrounding the implant can grow to become several hundred microns thick causing the implant to loosen and leading to clinical failure.
Bioactive bioceramics include hydroxyapatite, bioglass, and bioglass-ceramics. A “bioactive” material is one that elicits a specific biological response at its surface, which results in a beneficial biological and chemical reaction with the surrounding tissue. These reactions lead to chemical and biological bonding to the tissue at the interface between tissue and the bioactive implant, rather than mere ingrowth of tissue into pores of the implant, which only provide mechanical fixation. Hydroxyapatite (Ca10(PO4)6(OH)2, JC-PDS 9-432) has been of particular interest in orthopedic and dental application because the composition closely resembles native bone mineral and is inherently bioactive and osteoconductive. Though hydroxyapatite has the potential to be a load bearing implant material, applications have been limited to coatings, porous implants and as the bioactive phase in composites because most conventional calcium phosphate processing techniques have been unable to remove the process related defects in load bearing implants that result in poor mechanical properties. The problems associated with processing hydroxyapatite materials have been solved, at least in part, by the method disclosed in U.S. Pat. No. 6,013,591, which describes the synthesis of nanometer-sized hydroxyapatite grains that can be densified to form a hydroxyapatite structure with improved compressive strength, bending strength, and fracture toughness. These results can be attributed to the reduced flaw sizes inherent in nanocrystalline materials.
Resorbable bioceramics include tricalcium phosphate (TCP), calcium sulfate, and other calcium phosphate salt-based bioceramics. They are used to replace damaged tissue and are eventually resorbed such that host tissue replaces the implant. Problems long associated with resorbable bioceramics are the maintenance of strength, stability of the interface, and matching of the resorption rate to the regeneration rate of the host tissue. Furthermore, the constituents of resorbable biomaterials desirably are metabolically acceptable, since large quantities of material must be digested by cells. This imposes a severe limitation on these compositions. Calcium sulfate typically is used as a rapidly degrading bone filler in cases where mechanical strength is not necessary. α-TCP (α-Ca3 (PO4)2, JC-PDS 9-348) and β-TCP (β-Ca3(PO4)2, JC-PDS 9-169) typically are used when a rapidly degrading bone filler having more mechanical strength than calcium sulfate (CaSO4, JC-PDS 6-0046) is needed. Though calcium sulfate and TCP degrade rapidly, they both suffer from poor mechanical properties that have limited their applications to bone fillers.
Because calcium phosphate biomaterials are intrinsically bioactive and resorbable, they can be tailored for mechanical strength, resorption and bonding with the surrounding tissue through nanostructure. While α- and β-TCP are widely used and while a TCP formulation having mechanical and morphological properties advantageous for prostheses would be very useful, attempts to date have failed to produce reliable structural TCP implants. Accordingly, it is an object of the invention to provide techniques for synthesizing α- and β-TCP materials, and composites thereof, having structural and morphological properties useful for structural implants. In particular, it is an object of the invention to provide synthesis and processing techniques that produce a TCP material that can be densified under conditions that allow microstructural control, reduction or elimination of defects, ease of manufacture, and minimization of cost. It is another object of the invention to obtain TCP materials having enhanced mechanical properties, enhanced bioactivity/osteointegration and a controlled resorption profile by controlling the microstructure during sintering through crystal size, morphology and compositional control during synthesis and processing.